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This study was supported by the following: Fondo de Investigacion Sanitaria - FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI18/00044]; CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health initiative. MG-M was supported by a PFIS contract (FI19/00067) from the Fondo de Investigacion Sanitaria (Ministerio de Sanidad y Consumo, Spain). PM has a Miguel Servet contract funded by the ISCIII (CP16/00116), LdF was supported by ISCIII contract CA18/00017.

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Serum microRNAs Catalog Asthma Patients by Phenotype

Publicated to:JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY. 32 (6): 471-478 - 2022-01-01 32(6), DOI: 10.18176/jiaci.0753

Authors: Gil-Martínez M, Rodrigo-Muñoz JM, Sastre B, Cañas JA, García-Latorre R, Redondo N, de la Fuente L, Mínguez P, Mahíllo-Fernández I, Sastre J, Quirce S, Caballero ML, Olaguibel JM, Del Pozo V

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Abstract

Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients.Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed.Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma.hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

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